Apparatus and method for producing porous polymer particles

ABSTRACT

An apparatus and method for producing porous polymer particles is disclosed. The apparatus includes a rotating atomizer wheel ( 39 ) onto which a uniform thin layer of a polymer may be applied via a distributor ( 40 ), followed by the movement of the polymer to the periphery of the wheel due to centrifugal force and the subsequent release of free flying particles at the periphery of the wheel. The apparatus further includes a catch tray ( 14 ) to collect the porous polymer particles produced and an enclosure defining a partition between an interior environment and an exterior environment of the apparatus. The enclosure includes an aperture allowing a gaseous exchange between the interior and exterior environments.

This application is a National Stage Application of InternationalApplication Number PCT/CA01/01126, published, pursuant to PCT Article21(2).

FIELD OF THE INVENTION

The present invention relates to an apparatus and process for theformation of porous polymer particles for use in chromatographytechniques.

BACKGROUND

The capacity of certain porous support particles to cause selectiveretardation based on either size or shape is well known. Such particlesare used in chromatographic separation techniques, for example gelfiltration, to separate biological macromolecules, e.g. proteins, DNA,RNA polysaccharides and the like. The sieving particles arecharacterized by the presence of a microporous structure that exerts aselective action on the migrating solute macromolecules, restrictingpassage of larger particles more than that of the smaller particles.Thus, the utility of sieving lies in the capacity of the particles todistinguish between molecules of different sizes and shapes.

Affinity chromatography is a chromatographic method used for theisolation of proteins and other biological compounds. This technique isperformed using an affinity ligand attached to a support particle andthe resulting adsorbent packed into a chromatography column. The targetprotein is captured from solution by selective binding to theimmobilized ligand. The bound protein may be washed to remove unwantedcontaminants and subsequently eluted in a highly purified form.

Good separation using chromatography techniques depends on the size ofparticles, the size distribution of particles and the porosity of theparticles. The beads, once packed into a column, should be of a highstrength in order to support the liquid flow rates observed duringpurification and column regeneration. The effect of polymerconcentration and other preparation parameters on agarose particleporosity and strength are presented in S. Hjertén and K. O. Eriksson,Analytical Biochemistry, 137, 313–317 (1984), herein incorporated byreference. Additional fundamental information is presented in Studies onStructure and Properties of Agarose, A. S. Medin, pH.D. Thesis, Uppsala,1995, herein incorporated by reference. The description of chemicaladditives that help to improve the agarose particle porosity are foundin M. Letherby and D. A. Young, J. Chem. Soc., Faraday Trans. 1, 77,1953–1966 (1981) and in M. Tako and S. Nakamura, Carbohydrate Research,180, 277–284 (1988), both herein incorporated by reference.

Many particle formation methods and apparatus have been developed usingcentrifugal action to divide a liquid or into droplets or particles.Rotary atomizer machines in general are discussed in the text SprayDrying Handbook, K. Masters, Fifth edition, Longman Scientific &Technical, Longman Group UK Limited, herein incorporated by reference.Other relevant references related to atomization are Atomization andSprays, A. Lefebvre, Hemisphere Publications, 1989 and LiquidAtomization, L. Bayvel and Z. Orzechowski, Taylor and Francis, 1993,both herein incorporated by reference. A fundamental theory used in thepresent invention is known as “spray congealing”, based on spray dryingprinciples with the exception that solidification is the objectiveinstead of drying. Traditional emulsion based methods for agarose beadpreparation are described in, for example, Studies on Structure andProperties of Agarose, A. S. Medin, pH.D. Thesis, Uppsala, 1995 and in“The Preparation of Agarose Spheres for Chromatography of Molecules andParticles”, Biochimica et Biophysica Acta, 79, 393–398 (1964).

The particle size distribution produced by known apparatus and methodsrequire further sorting steps or procedures in order to select particlesof uniform size required for chromatography. The additional sortingsteps introduce further costs that could be avoided if the factorsdetermining size distribution of the particles and operating variablesare closely controlled. Without additional sorting steps, the productsmanufactured by conventional rotary atomization or emulsion techniquescannot be used in applications where the size distribution of theparticles must be very narrow. For example, when using particles inblood purification applications, small particles must be avoided assmall particles could be caught by the carrier fluid and would result incontamination of the purified material. Of course a narrow particle sizedistribution improves performances of particles in many applications,including chromatographic applications.

Operating variables that influence droplet size produced from atomizerwheels and hence particle size include speed of rotation, wheeldiameter, wheel design, feed rate, viscosity of feed and air, density offeed and air and surface tension of feed.

The atmosphere within which a particle passes is important in order toavoid reduction of pore size. In particular, humidity and temperaturecontrol avoids particle desiccation during polymerization and gellingstages. Particle desiccation reduces pore size. It is desirable to havea machine and process to produce particles using centrifugal action insuch a manner as that the particles have a narrow particle sizedistribution with both high porosity and flow.

Lengthy consideration of prior art devices and processes has identifieda number of factors that may be responsible for the wider sizedistribution of particles. Such factors include interruptions on thewheel surface that may impede radial acceleration of the particlesolution and adhesion to the surface of the wheel; lack of adequatetemperature control on the atomizer wheel that may result in changes infeed viscosity and particle structure; and uncontrolled airflow patternsat the perimeter of the atomizer wheel that may result in particletwinning due to collisions between particles prior to gelation and inundesired drying of the particles due to a modification in their pathdown from the wheel to the collecting liquid.

SUMMARY OF THE INVENTION

Applicants have recognized that control of humidity and temperaturewithin specific parameters in the immediate area of the atomizer wheelwill yield particles of a narrower size distribution than previouslypossible with both good porosity and rigidity.

Specifically, It has been discovered that the air flow rate, temperatureand humidity may be controlled in the immediate area of the atomizerwheel with sufficient accuracy to produce particles of a narrow sizedistribution. Control of temperature and humidity is achieved by thecombination of temperature and humidity control means and an enclosurecomprising an aperture, thus partially enclosing the atomizer machine.

The apparatus and method of the present invention produce particleshaving improved properties including very good bead shape and a narrowersize distribution than possible with conventional production apparatusand methods. The apparatus and method are particularly well suited forthe production of agarose beads for use in chromatography.

According to a first broad aspect, the invention provides an atomizermachine for the production of porous polymer particles, comprising:

-   a) an atomizer wheel having an edge, wherein the wheel is rotatable    about an axis;-   b) a distributor for depositing polymer in fluid state to the wheel;-   c) a catch tray disposed under the atomizer wheel to collect the    polymer particles formed as a result of ejection of the polymer from    the edge as the atomizer wheel rotates;-   d) an enclosure, enclosing the atomizer wheel, the distributor and    the catch tray, the enclosure defining a partition between an    interior environment of the atomizer machine and an exterior    environment of the atomizer machine;-   e) an aperture on the enclosure allowing a gaseous exchange between    the interior environment of the atomizer machine and the exterior    environment of the atomizer machine.

In an embodiment, the above-mentioned aperture is of variable size.

In an embodiment, the above-mentioned enclosure includes a peripheralwall surrounding the atomizer wheel, the distributor and the catch trayand a roof portion covering the peripheral wall.

In an embodiment, the above-mentioned peripheral wall is generallycircular.

In an embodiment, the above-mentioned aperture extends circumferentiallyalong the peripheral wall.

In an embodiment, the above-mentioned peripheral wall includes an upperportion and a lower portion, the aperture being defined between theupper portion and between the lower portion.

In an embodiment, the above-mentioned atomizer machine further comprisesan actuator to displace the upper portion and the lower portion withrelation to one another to vary the size of the aperture.

In an embodiment, the above-mentioned actuator is operative to displacethe upper portion along the axis to vary the size of the aperture.

In an embodiment, the above-mentioned atomizer machine includes atemperature control unit to regulate a level of temperature in theinterior environment.

In an embodiment, the above-mentioned atomizer machine includes ahumidity control unit to regulate a level of humidity in the interiorenvironment.

In an embodiment, the above-mentioned temperature control unit comprisesat least one of: a unit for controlling a size of the aperture, a unitfor controlling a level of temperature of the distributor and wheel, aunit for controlling a level of temperature and a flow rate of water inthe catch tray, at least one valve providing at least one respectivevapor stream at a periphery of the atomizer wheel, over the wheel and inthe enclosure, and at least one steam trap for de-misting air in theinterior environment and preventing water droplets from falling on theatomizer wheel.

In an embodiment, the above-mentioned humidity control unit comprises atleast one of: a unit for controlling a size of the aperture, a unit forcontrolling a level of temperature of the distributor and wheel, a unitfor controlling a level of temperature and a flow rate of water in thecatch tray, at least one valve providing at least one respective vaporstream at a periphery of the atomizer wheel, over the wheel and in theenclosure, and at least one steam trap for de-misting the air in theinterior environment and preventing water droplets from falling on theatomizer wheel.

In an embodiment, the above-mentioned atomizer machine further comprisesa monitor capable of indicating a level of temperature in the interiorenvironment.

In an embodiment, the above-mentioned atomizer machine further comprisesa monitor capable of indicating a level of humidity in the interiorenvironment.

In an embodiment, the above-mentioned atomizer machine further comprisesa trajectory control means to control a trajectory of the particles froma periphery of the atomizer wheel to the catch tray.

In an embodiment, the above-mentioned trajectory control means comprisesa unit for controlling a size of the aperture, disposing steam valves atthe periphery of the atomizer wheel, over the atomizer wheel anddirectly into the enclosure, and controlling airflow patterns at theperiphery of the atomizer wheel.

In an embodiment, the above-mentioned atomizer machine further comprisesa reactor for producing the polymer and at least one temperaturecontrolled conduit for feeding the polymer to the distributor.

In an embodiment, the above-mentioned at least one conduit consists of adouble jacket tube defining an inner passage for feeding the polymer tothe distributor and an outer envelope surrounding the inner passage,through which outer envelope a temperature liquid is flowed to control alevel of temperature of the polymer.

In an embodiment, the above-mentioned distributor rotates in the samedirection as the atomizer wheel.

In an embodiment, the above-mentioned distributor comprises a pluralityof holes.

In an embodiment, the above-mentioned plurality of holes are disposed ina circle.

In an embodiment, the above-mentioned distributor has 24 holes.

In an embodiment, the above-mentioned atomizer wheel has a flat surface.

In an embodiment, the above-mentioned atomizer machine further comprisesa shaft for receiving the atomizer wheel, the shaft being conical andtapered so as to reduce vibrations during rotation of the atomizerwheel.

In an embodiment, the above-mentioned atomizer machine further comprisesa shaft for receiving the atomizer wheel, the shaft having a threadedsection for securing the atomizer wheel to the shaft.

In an embodiment, the above-mentioned atomizer machine further comprisesa sorting bin for receiving and sorting the particles from the catchtray.

In an embodiment, the above-mentioned atomizer wheel has a perimeter,the perimeter having radially projecting teeth.

In an embodiment, the above-mentioned atomizer machine further comprisesat least one baffle disposed within the enclosure for regulating airflow within the internal environment.

In an embodiment, the above-mentioned at least one baffle is a pluralityof baffles.

In an embodiment, the above-mentioned plurality of baffles is 4 baffles.

According to a second broad aspect, the invention provides a method forproducing polymer particles, the method comprising:

-   a) providing an atomizer wheel, distributor and a catch tray    enclosed by an enclosure defining a partition between an interior    and an exterior environment and having an aperture for allowing    gaseous exchange between the interior and the exterior environment;    and-   b) allowing gaseous exchange through the aperture thereby to    regulate at least one condition of temperature, humidity or air flow    within the interior environment.

In an embodiment, the above-mentioned method further comprises varying asize of the aperture to vary a rate of gaseous exchange.

In a further embodiment, the above mentioned enclosure comprises a dome.The dome partially enclosing the atomizer machine at once creates anopen-system and creates a zone surrounding the machine. The open systemis necessary to obtain an air flow current from within the zone to theexterior of the zone. The air flow current contributes to the control oftemperature and humidity by preventing build-up of heat within theimmediate vicinity of the wheel as a result of rapid rotation of thewheel. The creation of a zone surrounding the machine is necessary todefine an area within which a desired temperature and humidity profilemay be maintained. It has been found that accurate control of thefactors that determine the temperature and humidity surrounding themachine is not possible in absence of a structure that defines a zonewithin which the temperature and humidity control means operate tomaintain the desired temperature and humidity profile. Advantageously,the dome is adjustable, thus providing adjustment of the aperture size,to compensate for variations in the factors that affect the temperatureand humidity in the immediate vicinity of the gel and particles.

Temperature, humidity and turbulence of the air surrounding theapparatus and inside the apparatus affect the properties of beads:porosity, flow, average particle size, particle size distribution, beadshape and non-specific binding.

In a further embodiment, the invention further provides an atomizermachine for the production of porous polymer particles having a narrowsize distribution comprising:

-   a) an atomizer wheel rotating about an axis;-   b) a distributor for providing a uniform thin layer of a gelatinous    polymer on the wheel;-   c) a shaft connecting the wheel to a rotor;-   d) a catch tray disposed under the wheel to collect the particles;-   e) a dome partially enclosing the atomizer wheel and catch tray so    as to maintain an open system and defining a zone surrounding the    wheel and catch tray;-   f) a means for temperature and humidity control for creating and    maintaining a temperature and humidity gradient within the zone;    wherein the gelatinous polymer deposited on the rotating wheel moves    to the periphery of the wheel under action of centrifugal force, the    film being broken into free flying particles at the edge of the    wheel.

These and other aspects of the invention shall become apparent to thoseof ordinary skill in the art upon consideration of the followingdescription of specific embodiments in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIG. 1 illustrates an apparatus for producing porous particles accordingto an embodiment of the invention;

FIG. 2 illustrates the central column of the apparatus of FIG. 1 showingbottom and top steam diffusers and shaft-wheel-distributor assembly;

FIG. 3A illustrates a toy plan view of the shaft-wheel-distributorassembly of FIG. 2;

FIG. 3B illustrates a side cut-away view of the shaft-wheel-distributorassembly of FIG. 3A.

FIG. 4A is a bottom plan view of the bottom steam diffuser of FIG. 2that distributes steam to the edge of the wheel;

FIG. 4B is a side cut-away view of the bottom steam diffuser of FIG. 4A;

FIG. 5 is a side view of the bottom steam diffuser of FIG. 2;

FIG. 6A is a top plan view of the top steam diffuser of FIG. 2;

FIG. 6B is a partial side cut-away view of the top steam diffuser ofFIG. 6A;

FIG. 7A is a bottom plan view of the top steam diffuser of FIG. 2;

FIG. 7B is a partial side cut-away view of the top steam diffuser ofFIG. 7A.

DETAILED DESCRIPTION OF THE INVENTION

One embodiment of the liquid atomization apparatus of the invention isillustrated in FIG. 1. A solution comprising a polymer is prepared inreactor (1). Solid particles are formed from the solution in a beader(2). A heated tube (12) connects the reactor (1) to the beader (2). Theapparatus and method of the invention will be described in conjunctionwith the production of agarose beads. However, the apparatus may be usedto produce particles of any other polymer.

The polymer is first slowly poured into a solvent, in an embodiment, atroom temperature, under vigorous stirring in a sealed stainless steelreactor (1), yielding a mixture. Suitable solvents include, but are notlimited to, water, aqueous salt solutions, and organic solvents. Themixture is heated up to over 90° C. to allow a complete dissolution ofthe agarose, forming a solution. The solution is quickly cooled down toan intermediate temperature between dissolution and gellingtemperatures, where a special additive can be added to the solution inorder to improve bead porosity. This additive or chemical can be anychemical that helps obtain improved porosity, such as a salt (forexample, ammonium sulfate) or a surfactant, in an embodiment, ammoniumsulfate. Then, the solution is slowly cooled down to the processtemperature, close enough to the gelling temperature, at a rate, forexample, of up to about 0.5° C./min, in an embodiment, not more than0.1° C./min.

Once the gel has reached its process temperature it is pumped through aheated conduit (12) consisting of a double jacket tube defining an innerpassage for feeding the polymer to the distributor and an outer envelopesurrounding the inner passage, through which outer envelope a liquid isflowed to control a level of temperature of the polymer from the reactor(1) to a nozzle (42), using a gear pump (11) also maintained at the gelprocess temperature by means of a pump head heater (not illustrated).The gel is supplied to a distributor (40) by the nozzle (42), and evenlydistributed on the atomization wheel (39) by means of a distributor(40). A thin uniform layer is formed by both centrifugal force and theuse of the distributor (40), and split by teeth (43) into filaments,which are broken in uniform sized spheres by the air flowing at theatomization wheel (39) edge. The beads travel through the surroundingair in the dome (13) aided by at least one, preferably four, baffles(35), where relative humidity and temperature are accurately controlled(from hot and humid at the atomization wheel (39) edge to less hot andless humid air at the catch tray (14) level) before they fall into thecatch tray (14). The temperature and humidity profiles in the dome (13),between the atomization wheel (39) and surface of the catch tray (45),are accurately controlled in order to make sure that the bead formedturns into a solid phase prior to reaching the catch tray surface. Aliquid, for example water, is continuously recirculated at a flow ratein a closed loop from the catch tray (14) to a sorting bin (20) and backto the catch tray via a recirculation pump (23). The low rate isadjusted in such a way that the surface of the catch tray (45) is alwayscovered with a thin continuous layer of liquid. A heat exchanger (21) isinstalled in the inlet reservoir (22) of the recirculation pump (23) tocontrol the catch tray (14) temperature. The beads can be collected atthe outlet of the sorting bin (20) in a sealed bucket (24) forpackaging.

The beader (2) thus contains a dome (13) and a catch tray (14). The dome(13) is not attached to the catch tray (14), leaving the beader (2) openfor air exchanges with the production room. The dome skirt (15) controlsthe gap between the dome (13) and the catch tray, which is responsiblefor the fresh air inlet into the process. Therefore, the dome (13)defines a zone surrounding the apparatus and partially encloses theatomizer wheel in an open system. In certain embodiments, thetemperature and humidity of the ambient air in the production roomshould be accurately controlled between 20–23° and 25–75% humidity,respectively, in order to get an adequate temperature and humidityprofile in the dome (13). In an embodiment, the subject inventionfurther comprises one or more monitors, as illustrated in FIGS. 1 and 2,capable of indicating a level of temperature and/or humidity in theinterior environment of the device. Deviations from these recommendedadjustments could be compensated by variations in other processparameters such as the gap between the dome (13) and the catch tray (14)as an example.

The catch tray (14), which has a slope from the center to the edge,collects the beads off the atomization wheel in a liquid that is incontinuous recirculation. In order to allow the dome to move up and downfor maintenance, cleaning and atomization wheel (39) installation, asystem of, for example, at least one rod with an air cylinder, forexample, three rods (18) with three air cylinders (19), may be used. Arigid structure (44) stabilizes the dome and avoids any instability thatcould result in vibration or movements of the dome (13).

Two columns are included in the beader: a top column (4), which isattached to the dome (13), and a bottom column (3), which is attached tothe catch tray (14). These two columns are clearly illustrated indrawings 2 to 7. The bottom column (3) holds the atomization wheel andhelps in the control of temperature and humidity profiles in the dome(13), while the top column (4) controls the environment over theatomization wheel and helps in the control of the temperature andhumidity in the dome (13). For maximum advantage, these two columnsshould be centered at all times. Both the rods (18) and the rigidstructure (44) of the dome (13) guarantee centering of the two columns(3) and (4). A main steam supply (5) is split in two steam lines (6) and(7), that are required for the control of both temperature and humidityin the dome (13).

A collecting liquid (water in the illustrated example) is distributedfrom the inlet reservoir (22) to the catch tray (14) through a splitter(16) which can be located at the center of the catch tray (14). Theliquid forms a uniform and evenly distributed thin film on the catchtray surface (45) and ends in tubes (17) that are connected to thesorting bin (20). For maximum advantage, the catch tray surface (45)should be continuously covered by a thin layer of liquid in order toprevent drying of the beads as they fall on the catch tray (14). Theliquid flow rate in the catch tray (14) and its temperature affect thecontrol of humidity and temperature in the dome (13).

The center part of the dome is illustrated in FIG. 2. A flat atomizationwheel (39) that, in certain embodiments, can have radially projectingteeth (43) at an edge thereof, is covered by a distributor (40), whichis centered with the atomization wheel (39) and, in certain embodiments,rotates at the same speed as the atomization wheel. A plate (58) isscrewed to the tapered shaft (29), keeping the atomizationwheel-distributor assembly in place. The distributor (40) is therecipient for the gel that comes out from a nozzle (42). The gel fallson a distributor lip (67), which is filled with holes (66), allowing thegel to be evenly distributed at the bottom of the distributor (40).These holes should occupy almost all the distributor lip (67) surfaceand be spaced in such a way that sufficient strength of the distributor(40) is maintained. An inside cylinder (60) of the distributor (40) islonger than an outside cylinder (59) giving a constant and reproduciblegap between the atomization wheel (39) and the distributor (40). Thisdesign avoids the use of spacers, which would unbalance the atomizationwheel-distributor assembly and increase particle size distribution. Inmounting high speed rotary bodies it is advantageous that the rotatingmass be balanced. A suitable mounting arrangement for securelypositioning the wheel on the rotatable shaft is to use a tapered shaft(29) in order to make atomization wheel-shaft alignment easy andreproducible and to maintain balancing. The inside of the atomizationwheel (39) is machined with the same slope as the tapered section (61)of the tapered shaft (29). In an embodiment, the atomization wheel (39)does not touch the bottom of the tapered section (61) but is supportedby the tapered section (61) itself. This has been designed to avoid anyscrewed part that would make the alignment difficult to reproduce. Formaximum advantage, the tapered shaft-atomization wheel-distributorassembly should be balanced, advantageously, at all speeds within therotation speed range utilized, to eliminate vibration.

The atomization wheel (39) stands over a bottom steam diffuser (31),which helps the regulation of temperature and humidity in the dome (13)and in the area close to the atomization wheel (39). The bottom steamdiffuser (31) is connected to a bottom steam line (7) where a steam trap(48) removes any steam condensate located in the bottom steam line (7).A needle valve (65), located as close as possible to the steam trap(48), accurately controls the steam flow rate to the bottom steamdiffuser (31). Steam is distributed into the dome (13) via slots (50)located on the side of the bottom steam diffuser (31). A bottom plate(46) and a top plate (38) are part of the bottom steam diffuser (31) andcan be affixed to it using screws (49), for example. A drain (47) allowsthe evacuation of any condensation that could occur in the bottom steamdiffuser (31) and avoids water accumulation that would result in steambubbling and result in a change in humidity and temperature conditionsin the dome (13). An annular plate (30) having holes, for example, verysmall holes, covers the side of the bottom steam diffuser (31). Thesmall holes of the annular plate (30) cover a limited sector of theannular plate (30). For example, the sector may be defined by the first60° starting at the bottom of the annular plate (30), in order to guidethe steam in the dome (13) and not under the atomization wheel (39) orat the atomization wheel (39) edge, close to the teeth (43). The bottomcolumn (3) also holds a motor (not illustrated) that controlsatomization wheel (39) RPMs (revolutions per minute).

The top steam diffuser (26) is connected to the top column (4) usingflange (28), spacer (25) and connection (27). The spacer (25) andconnection (27) avoid any chimney effect in the top column (4) thatcould result from the high spinning rate of the atomization wheel andthus affect the temperature and humidity conditions in the dome (13) andin the area close to and above the atomization wheel (39). The steam inthe top steam line (6) goes through a demister (69) where most waterdrops resulting from steam condensation are removed. A steam trap (68)completes condensate removal from the top steam line (6). The top steamline (6) is then split into three steam lines (8), (9) and (10), whereneedle valves (62), (63) and (64) respectively, accurately control thesteam flow rate in the areas of the top steam diffuser (26). The firststeam line (10) is split into a group of holes (55) located immediatelyabove the distributor (40), and keeps the air above the distributor (40)fully saturated in order to prevent the liquid sprayed from drying underthe effect of the fast air flow rate generated by pumping caused by therotation of the atomization wheel (39). The second steam line (9) issplit into a second group of holes (54) forming a circle located outsidethe distributor (40) but still above the atomization wheel (39). Thissecond steam line (9) is also required to avoid drying of the liquid onthe atomization wheel (39) but also to maintain the required temperatureprofile above the atomization wheel (39). A ring (57) restrictsexchanges between the dome (13) and the area above the atomization wheel(39) and helps to control temperature and humidity conditions above theatomization wheel (39). The third steam line (8) supplies steam to agroup of holes (53) located above the atomization wheel (39) but outsidethe ring (57), directing steam in the dome (13), close to theatomization wheel (39) edge.

The combination of appropriate adjustments to the following processparameters combined with the presence of a demister (69), steam traps(48) and (68), bottom steam diffuser (31) and top steam diffuser (26)controls the temperature and humidity profiles in the dome (13), in thearea above the atomization wheel and at the atomization wheel edge:distance between the dome (13) and the catch tray (14), steam pressure,temperature and flow rate of the liquid in the catch tray, humidity andtemperature of the air surrounding the apparatus (production room),needle valves (62), (63), (64), (65) adjustments, distance between theatomization wheel (39) and the ring (57) of the top steam diffuser (51),atomization wheel (39) spinning rate, distance between the atomizationwheel (39) and the surface of the catch tray (45). These parameterscontrol temperature and humidity profiles and are adjusted according tothe product manufactured and desired properties.

Although various embodiments of the invention are disclosed herein, manyadaptations and modifications may be made within the scope of theinvention in accordance with the common general knowledge of thoseskilled in this art. Such modifications include the substitution ofknown equivalents for any aspect of the invention in order to achievesubstantially the same result in substantially the same way. Numericranges are inclusive of the numbers defining the range. In the claims,the word “comprising” is used as an open-ended term, substantiallyequivalent to the phrase “including, but not limited to”. The followingexamples are illustrative of various aspects of the invention, and donot limit the broad aspects of the invention as disclosed herein.

In an embodiment, the atomizer machine includes a temperature controlunit to regulate a level of temperature in the interior environment.

In an embodiment, the atomizer machine includes a humidity control unitto regulate a level of humidity in the interior environment.

In an embodiment, the atomizer machine further comprises a sorting binfor receiving and sorting the particles from the catch tray.

In an embodiment, at least one conduit consists of a double jacket tubedefining an inner passage for feeding the polymer to the distributor andan outer envelope surrounding the inner passage, through which outerenvelope a temperature liquid is flowed to control a level oftemperature of the polymer.

EXAMPLES

Particles produced by the apparatus and method of the present inventionhave a very narrow size distribution as illustrated by the followingexamples describing agarose bead manufacture. The polymer preparationsteps and temperatures and most process parameters are specific toagarose preparation and could differ depending on the polymer used forparticle formation.

Example 1 Preparation of 4% 100 μm Agarose Beads

300 g of agarose was slowly poured in 4.25 L of purified water undervigorous mixing. This solution was heated up to 97–99° C. for 30 minutesand cooled down to 70° C. A heating/cooling fluid was used in the jacketof the reactor to control the temperature accurately. 750 mL of a 0.75Mammonium sulfate solution, maintained at 70° C., was added very slowlyand under vigorous stirring to the previous agarose solution in order toprevent local salting out, which would result in the formation of lumps.The final solution was cooled to 56–57° C. at a rate not more than 0.1°C./min.

In the meantime, the beader was started for stabilization. Atomizationwheel-column centering was checked, and the distance between theatomization wheel and the top column was adjusted to 15 mm. The domeopening (distance between the dome and the catch tray) was adjusted to 7cm. The atomization wheel speed was adjusted to 4900–5100 RPM , needlevalves were all adjusted at 7 and steam pressure was set at 5 psig atthe boiler outlet. These steam adjustments allowed the control of dometemperature at 36–39° C. close to the edge of the atomization wheel andwere adequate for the product manufactured and the size of the dome.Approximately 60 L/minute of purified water maintained at 16–19° C. wererecirculated in the catch tray to ensure that the catch tray surface iscontinuously covered with a thin film of water. This water flow rate isalso appropriated for the control of temperature and humidity in thedome. Resulting stabilized beader temperatures were the following:

-   Atomization wheel temperature: 56–60° C.-   Catch tray temperature: 16–19° C.-   Dome temperature close to the atomization wheel edge: 37–39° C.-   Temperature at area above atomization wheel: 71–73° C.

Once the beader was stabilized and the gel at the right temperature, thegear pump was turned on, feeding 1.6 L of gel/hr to the atomizationwheel. The following properties were recorded:

Speci- Lot Lot Lot Properties/Lot fications 000612381 001016434001017435 Porosity Thyroglobulin 0.35–0.53 0.44 0.48 0.48 Apoferritin0.50–0.76 0.60 0.63 0.64 β-Amylase 0.54–0.80 0.64 0.67 0.68 Alcohol0.58–0.86 0.69 0.72 0.72 Dehydrogenase Albumin 0.61–0.91 0.72 0.74 0.76(Bovine Serum) Carbonic 0.68–1.00 0.85 0.85 0.87 Anhydrase Pressure vsFlow >20 cm/hr 35 22 22 Particle Size Analysis Average N/A 106 103 101Size (μm) % Between N/A   98% 97.4%  90% 76–140 microns before sieving %Between Greater 99.7%   99%  99% 76–140 microns than 95% after sievingNon-Specific Less than 3.1 2.5 2.2 Binding 8 μg cyt./ml gel MicroscopyLess 0.89%  0.7% 0.9% than 3% broken, fused, damaged beadsProcess reproducibility has been demonstrated and is clearly documented.The particle size distribution before sieving is very narrow, a lot morethan any equivalent product available on the market at the moment. Thedistribution can be significantly improved by sieving, withoutsignificantly reducing the global yield. As an example, a 5 L batchprepared as above gave reproducibly 6.5 to 6.8 L of beads.

Example 2 Preparation of 4% 100 μm Agarose Beads Using Apparatus FurtherComprising Baffles

A plurality of 3 inch or 6 inch baffles were inserted into the dome inorder to get a more homogeneous temperature profile in the dome. Fourbaffles were equally distributed on the inside of the dome, vertically,to inhibit the effect of room conditions in the dome. With the bafflesin place, the dome is less sensitive to ambient conditions, and domeconditions are more easily reproduced. In addition, a wider range ofparticle size can be produced in the same apparatus when the baffles areused. The increase in disk RPM required to produce smaller particlesaffects the air pattern and hydrodynamics in the dome. The presence ofbaffles makes the temperature profiles less dependant on disk RPM. Also,the production of large particles (above 200 microns) resulted inprojection of particles on the walls of the dome, due to the inertia ofthe particles produced. The presence of baffles affects the air patternin such a way that the particles formed fall closer to the bottomcolumn, making possible the manufacture of large particles withoutchanging the design of the equipment.

4% 100 microns agarose beads have been manufactured using conditions inthe example above to demonstrate that the presence of baffles do notaffect particle properties. Lot 001103443 was manufactured using 6″baffles, while lot 001113447 was manufactured using 3″ baffles. Lot000612381 is reproduced in the table for comparison purposes.

Speci- Lot Lot Lot Properties/Lot fications 000612381 001113447001103443 Porosity Thyroglobulin 0.35–0.53 0.44 0.45 0.43 Apoferritin0.50–0.76 0.60 N/A N/A β-Amylase 0.54–0.80 0.64 N/A N/A Alcohol0.58–0.86 0.69 N/A N/A Dehydrogenase Albumin 0.61–0.91 0.72 N/A N/A(Bovine Serum) Carbonic 0.68–1.00 0.85 N/A N/A Anhydrase Pressure vsFlow >20 cm/hr 35 28 24 Particle Size Analysis Average N/A 106 101 100Size (μm) % Between N/A   98% 97.0% 97.2% 76–140 microns before sieving% Between Greater 99.7% 98.9% 98.6 76–140 microns than 95% after sievingNon-Specific Less than 3.1 N/A N/A Binding 8 μg cyt./ml gel MicroscopyLess 0.89%  1.9%  1.5% than 3% broken, fused, damaged beads

Example 3 Preparation of 5% 200 μm Agarose Beads

A procedure similar to the one described for the preparation of 4% 100microns agarose beads has been applied for the manufacturing of 200microns agarose beads at the 2 L scale. The differences are set forth inthe present description.

110 g of agarose was slowly poured in 1.7 L of purified water undervigorous mixing. This solution was heated up to 97–99° C. for 30 minutesand cooled down to 70° C. 300 mL of a 0.75M ammonium sulfate solution,maintained at 70° C., was added very slowly and under vigorous stirringto the previous agarose solution. The final solution was cooled to55–57° C. at a rate not more than 0.1° C./min.

In the meantime, the beader was started for stabilization. The distancebetween the atomization wheel and the top column was adjusted to 15 mm.The dome opening was adjusted to 4 cm. The atomization wheel speed wasadjusted to about 2000 RPM, needle valves were all adjusted at 3 andsteam pressure was set at 5 psig at the boiler outlet. These steamadjustments allowed the control of dome temperature at 47–50° C. closeto the edge of the atomization wheel and were adequate for the productmanufactured and the size of the dome.

Approximately 60 L/minute of purified water maintained at 14–16° C. wasrecirculated in the catch tray. Resulting stabilized beader temperatureswere the following:

-   Atomization wheel temperature: Not available due to the dome opening-   Catch tray temperature: 14–16° C.-   Dome temperature close to the atomization wheel edge: 47–50° C.-   Temperature at area above atomization wheel: 78–80° C.

Once the beader was stabilized and the gel at the right temperature, thegear pump was turned on, feeding about 2.8 L of gel/hr to theatomization wheel. The following properties were recorded:

Lot Lot Properties/Lot Specifications 001116450 001123453 PorosityThyroglobulin N/A 0.02 0.03 Apoferritin N/A 0.46 0.11 β-Amylase N/A 0.630.64 Alcohol N/A 0.70 0.73 Dehydrogenase Albumin N/A 0.71 0.74 (BovineSerum) Carbonic N/A 0.85 0.86 Anhydrase Pressure vs Flow N/A 114 106Particle Size Analysis Average N/A 200 199 Size (μm) % Between N/A N/AN/A 150–300 microns before sieving % Between N/A 96% 96% 150–300 micronsafter sieving Non-Specific N/A N/A N/A Binding Microscopy N/A 2.5 3.9

Example 4 Preparation of 4% 125 μm Agarose Beads

The procedure described for the production of 4% 100 microns agarosebeads has been applied for the production of 4% 125 microns agarosebeads at the 3 L scale. The differences are set forth in the presentdescription.

180 g of agarose was slowly poured in 2.55 L of purified water undervigorous mixing. This solution was heated up to 97–99° C. for 30 minutesand cooled down to 70° C. 450 mL of a 0.75M ammonium sulfate solution,maintained at 70° C., was added very slowly and under vigorous stirringto the previous agarose solution. The final solution was cooled to55–57° C. at a rate not more than 0.1° C./min.

In the meantime, the beader was started for stabilization. The distancebetween the atomization wheel and the top column was adjusted to 15 mm.The dome opening was adjusted to 7 cm. The atomization wheel speed wasadjusted to 3700–3800 RPM, needle valves were all adjusted at 4–5 andsteam pressure was set at 5 psig at the boiler outlet. These steamadjustments allowed the control of dome temperature at 35–37° C. closeto the edge of the atomization wheel and were adequate for the productmanufactured and the size of the dome. Approximately 60 L/minute ofpurified water maintained at 14–16° C. were recirculated in the catchtray. Resulting stabilized beader temperatures were the following:

-   Atomization wheel temperature: 56–58° C.-   Catch tray temperature: 14–16° C.-   Dome temperature close to the atomization wheel edge: 35–37° C.-   Temperature at area above atomization wheel: 71–75° C.

Once the beader was stabilized and the gel at the right temperature, thegear pump was turned on, feeding about 1.9 L of gel/hr to theatomization wheel. The following properties were recorded:

Speci- Lot Lot Lot Properties/Lot fications 010118464 010124465010125466 Porosity Thyroglobulin 0.35–0.53 0.45 0.47 0.48 Apoferritin0.50–0.76 N/A N/A N/A β-Amylase 0.54–0.80 N/A N/A N/A Alcohol 0.58–0.86N/A N/A N/A Dehydrogenase Albumin 0.61–0.91 N/A N/A N/A (Bovine Serum)Carbonic 0.68–1.00 N/A N/A N/A Anhydrase Pressure vs Flow >30 cm/hr 4453 45 Particle Size Analysis Average N/A 124 120 123 Size (μm) % BetweenN/A N/A N/A N/A 95–165 microns before sieving % Between Greater 99.5%98.5% 99.5% 95–165 microns than 95% after sieving Non-Specific Less thanN/A N/A N/A Binding 8 μg cyt./ml gel Microscopy Less 1.3 1.3 0.6 than 3%broken, fused, damaged beads

Example 5 Preparation of 4% 60 μm Agarose Beads

The procedure described for the production of 4% 100 microns agarosebeads has been applied for the production of 4% 60 microns agarose beadsat the 2 L scale. The differences are set forth in the presentdescription.

120 g of agarose was slowly poured in 1.7 L of purified water undervigorous mixing. This solution was heated up to 97–99° C. for 30 minutesand cooled down to 70° C. 300 mL of a 0.75M ammonium sulfate solution,maintained at 70° C., was added very slowly and under vigorous stirringto the previous agarose solution. The final solution was cooled to56–58° C. at a rate not more than 0.1° C./min.

In the meantime, the beader was started for stabilization. The distancebetween the atomization wheel and the top column was adjusted to 15 mm.The dome opening was adjusted to 7 cm. The atomization wheel speed wasadjusted to 7200 RPM , needle valves were all adjusted at 7 and steampressure was set at 5 psig at the boiler outlet. Those steam adjustmentsallowed the control of dome temperature at 33–35° C. close to the edgeof the atomization wheel and were adequate for the product manufacturedand the size of the dome. Approximately 60 L/minute of purified watermaintained at 16–19° C. were recirculated in the catch tray. Resultingstabilized beader temperatures were the following:

-   Atomization wheel temperature: 56–58° C.-   Catch tray temperature: 16–19° C.-   Dome temperature close to the atomization wheel edge: 33–35° C.-   Temperature at area above atomization wheel: 68–70° C.

Once the beader was stabilized and the gel at the right temperature, thegear pump was turned on, feeding about 0.6 L of gel/hr to theatomization wheel. The following properties were recorded:

Speci- Lot Lot Lot Properties/Lot fications 001018436 001019437001108446 Porosity Thyroglobulin >0.20 0.56 0.47 0.45 Apoferritin N/AN/A N/A N/A β-Amylase N/A N/A N/A N/A Alcohol N/A N/A N/A N/ADehydrogenase Albumin N/A N/A N/A N/A (Bovine Serum) Carbonic N/A N/AN/A N/A Anhydrase Pressure vs Flow >5 cm/hr 10 7 7 Particle SizeAnalysis Average N/A 59 61 59 Size (μm) % Between N/A 92.3% 90.5% 86.7%30–95 microns before sieving % Between N/A 91.3% 90.5% 90.5% 30–95microns after sieving Non-Specific N/A N/A N/A N/A Binding MicroscopyLess   0%  1.3%  0.8% than 3% broken, fused, damaged beadsAgain lot 001108446 was manufactured using the 6″ baffles as describedin the example above and compared to the standard material todemonstrate that the presence of baffles do not affect the particleproperties.

Example 6 Preparation of 6% 100 μm Agarose Beads

The procedure described for the production of 4% 100 microns agarosebeads has been applied for the production of 6% 100 microns agarosebeads at the 5 L scale. The differences are set forth in the presentdescription.

380 g of agarose was slowly poured in 4.25 L of purified water undervigorous mixing. This solution was heated up to 97–99° C. for 30 minutesand cooled down to 70° C. 750 mL of a 0.75M ammonium sulfate solution,maintained at 70° C., was added very slowly and under vigorous stirringto the previous agarose solution. The final solution was cooled to59–61° C. at a rate not more than 0.1° C./min.

In the meantime, the beader was started for stabilization. The distancebetween the atomization wheel and the top column was adjusted to 15 mm.The dome opening was adjusted to 7 cm. The atomization wheel speed wasadjusted to 4900–5100 RPM , needle valves were all adjusted at 7–9 andsteam pressure was set at 5 psig at the boiler outlet. Those steamadjustments allowed the control of dome temperature at 37–39° C. closeto the edge of the atomization wheel and were adequate for the productmanufactured and the size of the dome. Approximately 60 L/minute ofpurified water maintained at 16–20° C. were recirculated in the catchtray. Resulting stabilized beader temperatures were the following:

-   Atomization wheel temperature: 59–63-   Catch tray temperature: 16–20° C.-   Dome temperature close to the atomization wheel edge: 37–39° C.-   Temperature at area above atomization wheel: 71–74° C.

Once the beader was stabilized and the gel at the right temperature, thegear pump was turned on, feeding about 1.7 L of gel/hr to theatomization wheel. The following properties were recorded:

Lot Lot Properties/Lot Specifications Lot B28902 B32904 001026439Porosity Thyroglobulin 0.25–0.44 0.28 0.31 0.27 Apoferritin 0.39–0.590.44 0.47 N/A β-Amylase 0.48–0.72 0.50 0.52 N/A Alcohol 0.49–0.73 0.560.57 N/A Dehydrogenase Albumin 0.52–0.78 0.59 0.62 N/A (Bovine Serum)Carbonic 0.66–0.98 0.73 0.77 N/A Anhydrase Pressure vs Flow >45 cm/hr 6064 52 Particle Size Analysis Average N/A 101 101 102 Size (μm) % BetweenN/A 80.3 80.1   68% 76–140 microns before sieving % Between >95% 99% 99% 99.4% 76–140 microns after sieving Non-Specific Less than 8 μg 1.72.9 N/A Binding cyt./ml gel Microscopy Less than 3%  0% 0.3% 1.6 broken,fused, damaged beadsBatch 001026439 was produced using a higher pump flow rate. According tothe theory, the pump flow rate could be significantly increased withoutaffecting the product quality. This has been confirmed with lot001026439, where the pump was increased to its limit and deliveringabout 3.5 L/hr of gel on the atomization wheel without affecting theproperties only the particle size distribution before sieving wasslightly broader when the pump flow rate is increased, resulting in alower product yield. Therefore the gel flow rate fed to the atomizationdisk is not limited to the examples above, higher and lower feed ratescan result in the same product.

In an embodiment, the atomizer machine may further comprise at least onebaffle, in a further embodiment, a plurality of baffles, in a furtherembodiment, 4 baffles, which is/are disposed within the enclosure andcan affect/regulate the air pattern in the interior environment.

The particles produced by the apparatus and process of present inventionmay be used in all the chromatographic and electrophoretic methodologiesfor industrial purification purposes including affinity chromatography,gel filtration, ion-exchange chromatography, as support for graftingdifferent types of ligands; and coating rigid spheres of glass orplastic for types of chromatographic applications.

1. An atomizer machine for the production of porous polymer particles,comprising: a) an atomizer wheel having an edge, wherein said wheel isrotatable about an axis; b) a distributor for depositing polymer influid state to said wheel, wherein said distributor has a lip withholes, wherein the holes occupy almost all the distributor lip surfaceand are spaced in such a way that sufficient strength of the distributoris maintained; c) a catch tray disposed under the atomizer wheel tocollect the polymer particles formed as a result of ejection of thepolymer from the edge as the atomizer wheel rotates; d) an enclosure,enclosing said atomizer wheel, said distributor and said catch tray,said enclosure defining a partition between an interior environment ofsaid atomizer machine and an exterior environment of said atomizermachine and e) an aperture on said enclosure allowing a gaseous exchangebetween the interior environment of said atomizer machine and theexterior environment of said atomizer machine.
 2. The atomizer machineas defined in claim 1, wherein said aperture is of variable size.
 3. Theatomizer machine as defined in claim 2, wherein said enclosure includesa peripheral wall surrounding said atomizer wheel, said distributor andsaid catch tray and a roof portion covering said peripheral wall.
 4. Theatomizer machine as defined in claim 3, wherein said peripheral wall isgenerally circular.
 5. The atomizer machine as defined in claim 4,wherein said aperture extends circumferentially along said peripheralwall.
 6. The atomizer machine as defined in claim 4, wherein saidperipheral wall includes upper portion and a lower portion, saidaperture being defined between said upper portion and between said lowerportion.
 7. The atomizer machine as defined in claim 6, furthercomprising an actuator to displace said upper portion and said lowerportion with relation to one another vary the size of said aperture. 8.The atomizer machine as defined in claim 7, wherein said actuator isoperative to displace said upper portion along said axis to vary thesize of said aperture.
 9. The atomizer machine as defined in claim 2,including a temperature control unit to regulate a temperature in siadinterior environment.
 10. The atomizer machine as defined in claim 9,further comprising a monitor capable of indicating a level oftemperature in said interior environment.
 11. The atomizer machineaccording to claim 9, wherein water in recirculated at a flow rate in aclosed loop from the catch tray to a sorting bin and back to the catchtray via a recirculation pump, wherein the temperature control unitcomprises at least one of: a unit for controlling a size of saidaperture, a unit for controlling a level of temperature of thedistributor and wheel, a unit for controlling a level of temperature anda flow rate of water in the catch tray, at least one valve providing atleast one respective vapor stream at a periphery of said atomizer wheel.12. The atomizer machine as defined in claim 11, further comprising amonitor capable of indicating a level of temperature in said interiorenvironment.
 13. The atomizer machine as defined in claim 2, including ahumidity control unit to regulate a level of humidity in said interiorenvironment.
 14. The atomizer machine as defined in claim 13, furthercomprising a monitor capable of indicating a level of humidity in saidinterior environment.
 15. Thr atomize machine according to claim 13,wherein water is recirculated at a flow rate in a closed loop from thecatch tray to a sorting bin and back to the catch tray via arecirulation pump, wherein said humidity control unit comprises at leastone of: a unit for controlling a size of said aperture, a unit forcontrolling a level of temperatre of the distributor and wheel, a unitfor controlling a level of temperature and a flow rate of water in thecatch tray, at least one valve providing at least one respective vaporstream at a periphery of said atomizer wheel periphery, over the wheeland in the enclosure, and at least one steam trap for de-misting the airin the interior environment and preventing water droplets from fallingon said atomizer wheel.
 16. The atomizer machine as defined in claim 15,further comprising a monitor capable of indicating a level of humidityin said interior environment.
 17. The atomizer machine according toclaim 1, further comprising a trajectory control means to control atrajectory of the particles from a periphery of said atomizer wheel tosaid catch tray, and wherein the trajectory control means comprises aunit for controlling a size of said aperture, disposing steam valves orthe periphery of said atomizer wheel, over said atomizer wheel anddirectly into said enclosure, and controlling airflow patterns at theperiphery of said atomizer wheel.
 18. The atomizer machine according toclaim 1, further comprising a reactor for producing the polymer and atleast one temperature controlled conduit for feeding the polymer to thedistributor.
 19. The atomizer machine according to claim 18, wherein theat least one conduit consists of a double jacket tube defining an innerpassage for feeding the polymer to the distributor and an outer envelopesurrounding the inner passage, through which outer envelope atemperature liquid is flowed to control a level of temperature of thepolymer.
 20. The atomizer machine according to claim 1, wherein saiddistributor rotates in the same direction as said atomizer wheel. 21.The atomizer machine according to claim 1, wherein the distributorcomprises a plurality of holes.
 22. The atomizer machine according toclaim 21, wherein the pluralty of holes are disposed in a circle. 23.The atomizer machine according to claim 21, wherein the distributor has24 holes.
 24. The atomizer machine according to claim 1, wherein saidatomizer wheel has a flat surface.
 25. The atomizer machine according toclaim 1, further comprising a shaft for receiving said atomizer wheel,said shaft being conical and tapered so as to reduce vibrations duringrotation of said atomizer wheel.
 26. The atomizer machine according toclaim 1, further comprising a shaft for receiving said atomizer wheel,said shaft having a threaded section for securing said atomizer wheel tosaid shaft.
 27. The atomizer machine according to claim 1, furthercomprising a sorting bin for receiving and sorting the particles fromsaid catch tray.
 28. The atomizer machine according to claim 1, whereinsaid atomizer wheel has a perimeter, and wherein said atomizer wheel hasat said perimeter radially projecting teeth.
 29. The atomizer machineaccording to claim 1, further comprising at least one baffle disposedwithin the enclosure for regulating air flow within said internalenvironment.
 30. The atomizer machine according to claim 29, wherein theat least one baffle is a plurality of baffles.
 31. The atomizer machineaccording to claim 30, wherein the plurality of baffles comprisescomprises 4 baffles.
 32. A method for producing polymer particles, saidmethod comprising providing an atomizer machine comprising: a) anatomizer wheel having an edge, wherein said wheel is rotatable about anaxis; b) a distributor for depositing polymer in fluid state to saidwheel, wherein said distributor has a lip with holes, wherein the holesoccupy almost all the distributor lip surface and are spaced in such away that sufficient strength of the distributor is maintained; c) acatch tray disposed under the atomizer wheel to collect the polymerparticles formed as a result of ejection of the polymer from the edge asthe atomizer wheel rotates; d) an enclosure, enclosing said atomizerwheel, said distributor and said catch tray, said enclosure defining apartition between an interior environment of said atomizer machine andan exterior environment of said atomizer machine; and e) an aperture onsaid enclosure allowing a gaseous exchange between the interiorenvironment of said atomizer machine and the exterior environment ofsaid atomizer machine; and wherein said method further comprisesallowing gaseous exchange through said aperture thereby to regulate atleast one condition of temperture, humidity or air flow within saidinterior environment.
 33. The method of claim 32, further comprisingvarying a size of said aperture to vary a rate of gaseous exchange. 34.An atomizer machine for the production of porous polymer particlescomprising: a) an atomizer wheel having an edge, wherein said wheel isrotatable about an axis; b) a distributor for depositing polymer influid state to said wheel, wherein said distributor has a lip withholes, wherein the holes occupy almost all the distributor lip surfaceand are spaced in such a way that sufficient strength of the distributoris maintained; c) a catch tray disposed under the atomizer wheel tocollect the polymer particles formed as a result of ejection of thepolymer from the edge as the atomizer wheel rotates, wherein the surfaceof the catch tray is covered with a layer of liquid; d) an enclosure,enclosing said atomizer wheel, said distributor and said catch tray,said enclosure defining a partition between an interior environment ofsaid atomizer machine and an exterior environment of said atomizermachine; and e) an aperture on said enclosure allowing a gaseousexchange between the interior environment of said atomizer machine andthe exterior environment of said atomizer machine.
 35. An atomizermachine for the production of porous polymer paiticles, comprising: a)an atomizer wheel having an edge, wherein said wheel is rotatable aboutan axis; b) a distributor for depositing polymer in fluid state to saidwheel, wherein said distributor has a lip with holes, wherein the holesoccupy almost all the distributor lip surface and are spaced in such away that sufficient strength of the distributor is maintained; c) acatch tray disposed under the atomizer wheel to collect the polymerparticles formed as a result of ejection of the polymer from the edge asthe atomizer wheel rotates, wherein the temperature of the catch tray iscontrolled by a heat exchanger; d) an enclosure, enclosing said atomizerwheel, said distributor and said catch tray, said enclosure defining apartition between an interior environment of said atomizer machine andan exterior environment of said atomizer machine; and e) an aperture onsaid enclosure allowing a gaseous exchange between the interiorenvironment of said atomizer machine and the exterior environment ofsaid atomizer machine.